The use of iodine as an aerial disinfectant has been advocated at least since 1926. Iodine is also known to be useful in disinfecting drinking water. Iodine can inactivate viruses over a wide range of water quality.
Johansson, U.S. Pat. No. 4,010,259, described methods and materials for complexing iodine with various iodophors. The iodophors of the '259 patent are described as those in which the iodine is non-covalently bonded to a hydrophilic organic carrier. The organic carrier is insoluble and may exhibit ion exchange groups in water, but capable of swelling in water to form a gel. U.S. Pat. Nos. 5,360,605 and 5,370,869 represent that iodine complexed with polyvinyl pyrrolidone ("PVP", e.g., povidone USP), is an effective iodophor for killing or inactivating certain pathogens in biological fluids, particularly platelet-bearing fluid.
Disinfection of water by the use of iodine bound to anion exchange resins has been described by Hatch (U.S. Pat. No. 4,594,392; U.S. Pat. No. 4,190,529 and Ind. Eng. Chem. Prod. Res. Dev. 20 (1981) 392-385); and Gartner (U.S. Pat. No. 4,420,590).
It has also been found that certain iodinated matrices can disinfect biological fluids, i.e., fluids containing labile, biologically active components such as proteins, particularly blood derived proteins. Such iodinated matrices are disclosed in U.S. patent application Ser. No. 08/813,337, filed Mar. 7, 1997, (which corresponds to WO 97/48482) which is a continuation in part application of U.S. patent application Ser. No. 08/667,448, filed Jun. 21, 1996 (which corresponds to WO 97/48422) both of which are incorporated herein by reference.
Until recently, it was believed that such matrices required direct contact or substantial proximity with the proteins of the biological fluid. For example, it is known that iodine species complex with amine groups to form iodamines. Gottardi, W., Iodine and Iodine Compounds in Disinfection, Sterilization, and Preservation, (Block, Seymour S., Ed.) Lea & Febiger, Philadelphia (3d ed., 1983). Further, such iodamines can be formed by reaction of iodine with the amine residue in proteins. When exposed to proteinaceous fluids, iodinated matrices might create an iodamine reservoir that releases iodine into the fluid over extended periods thereby disinfecting the fluid. Thus, one of skill in the art would expect that such solution phase effects in iodinated matrices are influenced by the presence of protein, and might even be protein-dependent.
Until recently, it was also believed that such iodinated matrices exerted their pathogen inactivation effect only through direct contact with the solution containing the organism to be inactivated. During this time of direct contact, the organism was thought to be inactivated by exposure to the high levels of iodine present on the matrix.
The direct contact method, however, presents potential drawbacks. Generally, proteins are ionic and thus under certain conditions can bind to ionic exchange matrices. If a protein of interest were to bind to an iodinated matrix, it would be subjected to short term exposure to high concentrations of iodine. The ionic composition and pH of the protein solution must be tailored to prevent such binding. This places limits on the solution conditions useful in the direct contact method.
It has now been discovered that non-proteinaceous fluids, such as water and other polar solvents, can extract a pathogen inactivating agent from iodinated ion exchange matrices. The resulting pathogen inactivating composition (or "PIC") contains a water soluble pathogen inactivating agent that can be readily separated from the iodinated matrix material, stored, and subsequently used to disinfect biological fluids. Compared to methods requiring that the biological fluid directly contact the iodinated matrix (see, e.g., WO97 48422 and WO97 48482), PICs provide a more mild and facile means for disinfection. The PICs of the invention are more convenient in application, and reduce the likelihood that proteins will be denatured or otherwise destroyed during disinfection.